Germ Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms

Malkin, David; Li, Frederick P.; Strong, Louise C.; Fraumeni, Joseph F.; Nelson, Camille E.; Kim, David H.; Kassel, Jayne; Gryka, Magdalena A.; Bischoff, Farideh Z.; Tainsky, Michael A.; Friend, Stephen H.

doi:10.1126/science.1978757

Cited by 3,765Cancer-related Molecular PathwaysGenetic factors in colorectal cancerBRCA gene mutations in cancer

Germ Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms

Malkin, David, Li, Frederick P., Strong, Louise C., Fraumeni, Joseph F., Nelson, Camille E., Kim, David H., Kassel, Jayne, Gryka, Magdalena A. +3 more·1990·Science

DOI 10.1126/science.1978757

Open this paper in CoChat — free account

Abstract

Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.

Integrity signals

Registry

Crossref · 10.1126/science.1978757

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Germline TP53 mutations produce a somewhat different tissue distribution of cancers than sporadic TP53-mutant cancers.
“In the case of the classical tumor suppressor gene TP53, germline mutations result in a somewhat different tissue distribution of cancers than sporadic TP53-mutant cancers in patients who lack germline mutations (7).”
From Metabolic reprogramming and cancer progression (2020) · cites this paper as [7]

A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma
Friend, S. H., Bernards, R., Rogelj, S., Weinberg, R. A., Rapaport, J. M., Albert, D. M., & Dryja, T. P. (1986) · Nature · doi:10.1038/323643a0 · Cited by 2,948 · see citing works
Self-citation
Mutations in the p53 gene occur in diverse human tumour types
Nigro, J. M., Baker, S. J., Preisinger, A. C., Jessup, J. M., Hosteller, R., Cleary, K. R., Signer, S. H., Davidson, N. E., Baylin, S., Devilee, P., et al. (1989) · Nature · doi:10.1038/342705a0 · Cited by 2,730 · see citing works
Chromosome 17 Deletions and p53 Gene Mutations in Colorectal Carcinomas
Baker, S. J., Fearon, E. R., Nigro, J. M., Hamilton, S. R., Preisinger, A. C., Jessup, J. M., vanTuinen, P., Ledbetter, D. H., Barker, D. F., Nakamura, Y., et al. (1989) · Science · doi:10.1126/science.2649981 · Cited by 2,067 · see citing works
The p53 proto-oncogene can act as a suppressor of transformation
Finlay, C. A., Hinds, P. W., & Levine, A. J. (1989) · Cell · doi:10.1016/0092-8674(89)90045-7 · Cited by 1,987 · see citing works
Soft-Tissue Sarcomas, Breast Cancer, and Other Neoplasms
Li, F. P., & FRAUMENI, J. F. (1969) · Annals of Internal Medicine · doi:10.7326/0003-4819-71-4-747 · Cited by 1,514 · see citing works
Self-citation
A cancer family syndrome in twenty-four kindreds.
Li, F. P., Fraumeni, J. F., Mulvihill, J. J., Blattner, W. A., Dreyfus, M., Tucker, M., & Miller, R. (1988) · PubMed · Cited by 1,293 · see citing works
Self-citation
p53: A Frequent Target for Genetic Abnormalities in Lung Cancer
Takahashi, T., Nau, M. M., Chiba, I., Birrer, M. J., Rosenberg, R. K., Vinocour, M., Levitt, M. L., Pass, H. I., Gazdar, A. F., & Minna, J. D. (1989) · Science · doi:10.1126/science.2554494 · Cited by 1,196 · see citing works
Activating Mutations for Transformation by p53 Produce a Gene Product That Forms an hsc70-p53 Complex with an Altered Half-Life
Finlay, C. A., Hinds, P. W., Tan, T., Eliyahu, D., Oren, M., & Levine, A. J. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.2.531 · Cited by 1,144 · see citing works
Increased expression of mutant forms of p53 oncogene in primary lung cancer
Iggo, R. D., Bártek, J., Lane, D. P., Gatter, K. C., Harris, A. L., & Bártek, J. (1990) · The Lancet · doi:10.1016/0140-6736(90)90801-b · Cited by 1,030 · see citing works
p53 Functions as a Cell Cycle Control Protein in Osteosarcomas
Diller, L., Kassel, J., Nelson, C. E., Gryka, M. A., Litwak, G., Gebhardt, M. C., Bressac, B., Öztürk, M., Baker, S. J., Vogelstein, B., et al. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.11.5772 · Cited by 775 · see citing works
Self-citation
Chromosomal Imbalance in the Aniridia-Wilms' Tumor Association: 11p Interstitial Deletion
Riccardi, V. M., Sujansky, E., Smith, A. C. M., et al. (1978) · PEDIATRICS · doi:10.1542/peds.61.4.604 · Cited by 728 · see citing works
Wild-type p53 can inhibit oncogene-mediated focus formation.
Eliyahu, D., Michalovitz, D., Eliyahu, S., Pinhasi-Kimhi, O., & Oren, M. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.22.8763 · Cited by 681 · see citing works
Structural aspects of the p53 protein in relation to gene evolution.
Soussi, T., de Fromentel, C. C., & May, P. (1990) · PubMed · Cited by 608 · see citing works
Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines.
Bártek, J., Iggo, R. D., Gannon, J., & Lane, D. P. (1990) · PubMed · Cited by 603 · see citing works
Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation
Hinds, P. W., Finlay, C. A., & Levine, A. J. (1989) · Journal of Virology · doi:10.1128/jvi.63.2.739-746.1989 · Cited by 595 · see citing works
Localization of gene for human p53 tumour antigen to band 17p13
Isobe, M., Emanuel, B. S., Givol, D., Oren, M., & Croce, C. M. (1986) · Nature · doi:10.1038/320084a0 · Cited by 485 · see citing works
Mutant p53 DNA clones from human colon carcinomas cooperate with ras in transforming primary rat cells: a comparison of the "hot spot" mutant phenotypes.
Hinds, P. W., Finlay, C. A., Quartin, R. S., Baker, S. J., Fearon, E. R., Vogelstein, B., & Levine, A. J. (1990) · PubMed · Cited by 408 · see citing works
Aniridia-Wilms’ tumor association: evidence for specific deletion of 11p13
Francke, U., Holmes, L. B., Atkins, L., et al. (2008) · Cytogenetics and Cell Genetics · doi:10.1159/000131375 · Cited by 401 · see citing works
Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis.
Menon, A. G., Anderson, K. M., Riccardi, V. M., Chung, R. Y., Whaley, J. M., Yandell, D. W., Farmer, G. E., Freiman, R. N., Lee, J. K., & Li, F. P. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.14.5435 · Cited by 396 · see citing works
Self-citation
High Incidence of Lung, Bone, and Lymphoid Tumors in Transgenic Mice Overexpressing Mutant Alleles of the p53 Oncogene
Lavigueur, A., Maltby, V., Mock, D., Rossant, J., Pawson, T. J., & Bernstein, A. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.9.3982 · Cited by 393 · see citing works
Alterations in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia.
Ahuja, H., Bar‐Eli, M., Advani, S. H., Benchimol, S., & Cline, M. J. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.17.6783 · Cited by 284 · see citing works
A variation in the structure of the protein-coding region of the human p53 gene
Buchman, V. L., Chumakov, P. M., Ninkina, N. N., Samarina, O. P., & Georgiev, G. P. (1988) · Gene · doi:10.1016/0378-1119(88)90196-5 · Cited by 278 · see citing works
Mechanisms of p53 loss in human sarcomas.
Mulligan, L. M., Matlashewski, G., Scrable, H. J., & Cavenee, W. K. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.15.5863 · Cited by 268 · see citing works
Prediction of the Risk of Hereditary Retinoblastoma, Using DNA Polymorphisms within the Retinoblastoma Gene
Wiggs, J. L., Nordenskjöld, M., Yandell, D. W., Rapaport, J., Grondin, V., Janson, M., Werelius, B., Petersen, R., Craft, A. W., Riedel, K., et al. (1988) · New England Journal of Medicine · doi:10.1056/nejm198801213180305 · Cited by 242 · see citing works
Immunological evidence for the association of p53 with a heat shock protein, hsc70, in p53-plus-ras-transformed cell lines.
Hinds, P. W., Finlay, C. A., Frey, A. B., & Levine, A. J. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.8.2863 · Cited by 232 · see citing works
Prospective Study of a Family Cancer Syndrome
Li, F. P. (1982) · JAMA · doi:10.1001/jama.1982.03320440040031 · Cited by 229 · see citing works
Self-citation
Mutant p53 proteins bind hsp 72/73 cellular heat shock-related proteins in SV40-transformed monkey cells.
Hw, S., Chumakov, P. M., Wj, W., et al. (1987) · PubMed · Cited by 163 · see citing works
Cancer in Survivors of Childhood Soft Tissue Sarcoma and Their Relatives
Strong, L. C., Stine, M. D., & Norsted, T. L. (1987) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/79.6.1213 · Cited by 141 · see citing works
Self-citation
Identification and characterization of a p53 gene mutation in a human osteosarcoma cell line.
Romano, J., Ehrhart, J., Duthu, A., et al. (1989) · PubMed · Cited by 96 · see citing works
Isolation and mapping of a polymorphic DNA sequence (pYNZ22) on chromosome 17p [D17S30]
Nakamura, Y., Ballard, L., Leppert, M., O'Connell, P., Lathrop, M. G., Lalouel, J.-M., & White, R. L. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.12.5707 · Cited by 92 · see citing works
Excess risk of breast cancer in the mothers of children with soft tissue sarcomas
Birch, J. M., Hartley, A. L., Marsden, H. B., et al. (1984) · British Journal of Cancer · doi:10.1038/bjc.1984.51 · Cited by 75 · see citing works
Identification of factors associated with high breast cancer risk in the mothers of children with soft tissue sarcoma.
Birch, J. M., Hartley, A. L., Blair, V., et al. (1990) · Journal of Clinical Oncology · doi:10.1200/jco.1990.8.4.583 · Cited by 25 · see citing works
BanII and ScaI RFLPs at the human p53 gene locus
Masharani, U. B., Wolf, D., & Frossard, P. M. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.15.7757 · Cited by 16 · see citing works
[A cancer family].
Jc, D., Lavigne, F., & Mensah, A. (1979) · PubMed · Cited by 3 · see citing works

Flagged first, then by citations

Sorted by citations

p53 Mutations in Human Cancers
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991) · Science · doi:10.1126/science.1905840 · Cited by 8,018 · see citing works
A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia
Kastan, M. B., Zhan, Q., El-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., Plunkett, B. S., Vogelstein, B., & Fornace, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90593-2 · Cited by 3,047 · see citing works
Metabolic reprogramming and cancer progression
Faubert, B., Solmonson, A., & DeBerardinis, R. J. (2020) · Science · doi:10.1126/science.aaw5473 · Cited by 2,740 · see citing works
TP53 mutations in human cancers: origins, consequences, and clinical use.
Olivier, M., Hollstein, M., & Hainaut, P. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001008 · Cited by 2,199 · see citing works
Molecular Basis of Colorectal Cancer
Markowitz, S. D., & Bertagnolli, M. M. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804588 · Cited by 2,052 · see citing works
The first 30 years of p53: growing ever more complex.
Levine, A. J., & Oren, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2723 · Cited by 1,967 · see citing works
The p53 pathway: positive and negative feedback loops
Harris, S. L., & Levine, A. J. (2005) · Oncogene · doi:10.1038/sj.onc.1208615 · Cited by 1,967 · see citing works
Putting p53 in context
Kastenhuber, E. R., & Lowe, S. W. (2017) · Cell · doi:10.1016/j.cell.2017.08.028 · Cited by 1,906 · see citing works
Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database
Petitjean, A., Mathe, E., Kato, S., Ishioka, C., Tavtigian, S. V., Hainaut, P., & Olivier, M. (2007) · Human Mutation · doi:10.1002/humu.20495 · Cited by 1,598 · see citing works
“Inherited TP53 mutations predispose to a wide spectrum of early-onset cancers and are associated with Li-Fraumeni and Li-Fraumeni-like syndrome (LFS and LFL, respectively) [Malkin et al., 1990].”
Background
Association of BRCA1 with Rad51 in Mitotic and Meiotic Cells
Scully, R., Chen, J., Plug, A., Xiao, Y., Weaver, D., Feunteun, J., Ashley, T., & Livingston, D. M. (1997) · Cell · doi:10.1016/s0092-8674(00)81847-4 · Cited by 1,459 · see citing works
How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression
Aubrey, B. J., Kelly, G. L., Janic, A., Herold, M. J., & Strasser, A. (2018) · Cell Death & Differentiation · doi:10.1038/cdd.2017.169 · Cited by 1,395 · see citing works
A Single Nucleotide Polymorphism in the MDM2 Promoter Attenuates the p53 Tumor Suppressor Pathway and Accelerates Tumor Formation in Humans
Bond, G. L., Hu, W., Bond, E. E., Robins, H., Lutzker, S. G., Arva, N. C., Bargonetti, J., Bartel, F., Taubert, H., Wuerl, P., et al. (2004) · Cell · doi:10.1016/j.cell.2004.11.022 · Cited by 1,265 · see citing works
Self-citation
Autophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182 · see citing works
When mutants gain new powers: News from the mutant p53 field
Brosh, R., & Rotter, V. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2693 · Cited by 1,132 · see citing works
Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome
Lang, G. A., Iwakuma, T., Suh, Y.-A., Liu, G., Rao, V. A., Parant, J. M., Valentin-Vega, Y. A., Terzian, T., Caldwell, L. C., Strong, L. C., et al. (2004) · Cell · doi:10.1016/j.cell.2004.11.006 · Cited by 1,069 · see citing works
Self-citation
Targeting p53 pathways: mechanisms, structures, and advances in therapy
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01347-1 · Cited by 1,016 · see citing works
The MDM2 gene amplification database
Momand, J. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.15.3453 · Cited by 982 · see citing works
Targeting mutant p53 for efficient cancer therapy
Bykov, V. J. N., Eriksson, S. E., Bianchi, J., & Wiman, K. G. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.109 · Cited by 889 · see citing works
Induction of medulloblastomas in p53 -null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum
Marino, S., Vooijs, M., van der Gulden, H., Jonkers, J., & Berns, A. (2000) · Genes & Development · doi:10.1101/gad.14.8.994 · Cited by 920 · see citing works
TP53 mutations in human cancers: Functional selection and impact on cancer prognosis and outcomes
Petitjean, A., Achatz, M. I. W., Borresen-Dale, A. L., Hainaut, P., & Olivier, M. (2007) · Oncogene · doi:10.1038/sj.onc.1210302 · Cited by 884 · see citing works
Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations
Rausch, T., Jones, D. T. W., Zapatka, M., Stütz, A. M., Zichner, T., Weischenfeldt, J., Jäger, N., Remke, M., Shih, D., Northcott, P. A., et al. (2012) · Cell · doi:10.1016/j.cell.2011.12.013 · Cited by 865 · see citing works
Self-citation
A role for both RB and p53 in the regulation of human cellular senescence*1
SHAY, J. (1991) · Experimental Cell Research · doi:10.1016/0014-4827(91)90453-2 · Cited by 757 · see citing works
TP53Variations in Human Cancers: New Lessons from the IARC TP53 Database and Genomics Data: Human Mutation
Bouaoun, L., Sonkin, D., Ardin, M., Hollstein, M., Byrnes, G., Zavadil, J., & Olivier, M. (2016) · Human Mutation · doi:10.1002/humu.23035 · Cited by 730 · see citing works
Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers
Bougeard, G., Renaux-Petel, M., Flaman, J.-M., Charbonnier, C., Fermey, P., Belotti, M., Gauthier-Villars, M., Stoppa-Lyonnet, D., Consolino, E., Brugières, L., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.5728 · Cited by 760 · see citing works
New Horizons in the Treatment of Osteosarcoma
Meltzer, P. S., & Helman, L. J. (2021) · New England Journal of Medicine · doi:10.1056/nejmra2103423 · Cited by 672 · see citing works
MDMX: a novel p53‐binding protein with some functional properties of MDM2.
Shvarts, A., Steegenga, W. T., Riteco, N., van Laar, T., Dekker, P., Bazuine, M., van Ham, R. C., van der Houven van Oordt, W., Hateboer, G., van der Eb, A. J., et al. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00919.x · Cited by 648 · see citing works
Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy
Shangary, S., & Wang, S. (2009) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094723 · Cited by 623 · see citing works
Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases
Stratton, M. R. (1997) · The Lancet · doi:10.1016/s0140-6736(96)10109-4 · Cited by 579 · see citing works
Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice.
Harvey, M., McArthur, M. J., Montgomery, C. A., Butel, J. S., Bradley, A., & Donehower, L. A. (1993) · Nature Genetics · doi:10.1038/ng1193-225 · Cited by 542 · see citing works
An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma
Ribeiro, R. C., Sandrini, F., Figueiredo, B., Zambetti, G. P., Michalkiewicz, E., Lafferty, A. R., DeLacerda, L., Rabin, M., Cadwell, C., Sampaio, G., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161479898 · Cited by 541 · see citing works
Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome
Kratz, C. P., Achatz, M. I., Brugières, L., Frebourg, T., Garber, J. E., Greer, M.-L. C., Hansford, J. R., Janeway, K. A., Kohlmann, W. K., McGee, R., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0408 · Cited by 534 · see citing works
Self-citation
Coping with stress: multiple ways to activate p53
Horn, H. F., & Vousden, K. H. (2007) · Oncogene · doi:10.1038/sj.onc.1210263 · Cited by 522 · see citing works
Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others
Sabapathy, K., & Lane, D. P. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.151 · Cited by 517 · see citing works
Relative frequency and morphology of cancers in carriers of germline TP53 mutations
Birch, J. M., Alston, R. D., McNally, R. J., Evans, D. G. R., Kelsey, A. M., Harris, M., Eden, O. B., & Varley, J. M. (2001) · Oncogene · doi:10.1038/sj.onc.1204621 · Cited by 467 · see citing works
The p53 network: cellular and systemic DNA damage responses in aging and Cancer
Reinhardt, H. C., & Schumacher, B. (2012) · Trends in Genetics · doi:10.1016/j.tig.2011.12.002 · Cited by 458 · see citing works
p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts.
Harvey, D. M., & Levine, A. J. (1991) · Genes & Development · doi:10.1101/gad.5.12b.2375 · Cited by 453 · see citing works
Hereditary breast and ovarian cancer: new genes in confined pathways
Nielsen, F. C., van Overeem Hansen, T., & Sørensen, C. S. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.72 · Cited by 367 · see citing works
Loss of Rb activates both p53‐dependent and independent cell death pathways in the developing mouse nervous system.
Macleod, K. F., Hu, Y., & Jacks, T. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01006.x · Cited by 321 · see citing works
Common Musculoskeletal Tumors of Childhood and Adolescence
Arndt, C. A. S., Rose, P. S., Folpe, A. L., & Laack, N. N. (2012) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2012.01.015 · Cited by 298 · see citing works
MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner
Bond, G. L., Hirshfield, K. M., Kirchhoff, T., Alexe, G., Bond, E. E., Robins, H., Bartel, F., Taubert, H., Wuerl, P., Hait, W., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0180 · Cited by 287 · see citing works
Are there low-penetrance TP53 alleles? Evidence from childhood adrenocortical tumors
Varley, J. M., McGown, G., Thorncroft, M., James, L. A., Margison, G. P., Forster, G., Evans, D. G. R., Harris, M., Kelsey, A. M., & Birch, J. M. (1999) · The American Journal of Human Genetics · doi:10.1086/302575 · Cited by 266 · see citing works
Effects of genetic background on tumorigenesis in p53‐deficient mice
Donehower, L. A., Harvey, M., Vogel, H., McArthur, M. J., Montgomery, C. A., Park, S. H., Thompson, T., Ford, R. J., & Bradley, A. (1995) · Molecular Carcinogenesis · doi:10.1002/mc.2940140105 · Cited by 252 · see citing works
Smoking, p53 Mutation, and Lung Cancer
Gibbons, D. L., Byers, L. A., & Kurie, J. M. (2014) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-13-0539 · Cited by 255 · see citing works
p53 is frequently mutated in Burkitt's lymphoma cell lines
Farrell, P. J., Allan, G. J., Shanahan, F., Vousden, K. H., & Crook, T. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07837.x · Cited by 254 · see citing works
A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome
Wooster, R., Mangion, J., Eeles, R., Smith, S., Dowsett, M., Averill, D., Barrett-Lee, P., Easton, D. F., Ponder, B. A. J., & Stratton, M. R. (1992) · Nature Genetics · doi:10.1038/ng1092-132 · Cited by 250 · see citing works
Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families
Bougeard, G., Sesboüé, R., Baert-Desurmont, S., Vasseur, S., Martin, C., Tinat, J., Brugières, L., Chompret, A., Paillerets, B. B.-D., Stoppa-Lyonnet, D., et al. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2008.057570 · Cited by 230 · see citing works
Management of adrenocortical carcinoma
Allolio, B., Hahner, S., Weismann, D., & Fassnacht, M. (2004) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2003.01881.x · Cited by 214 · see citing works
An inherited mutation outside the highly conserved DNA-binding domain of the p53 tumor suppressor protein in children and adults with sporadic adrenocortical tumors
Latronico, A. C., Pinto, E. M., Domenice, S., Fragoso, M. C. B. V., Martin, R. M., Zerbini, M. C., Lucon, A. M., & Mendonca, B. B. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7957 · Cited by 224 · see citing works
Synthetic small inhibiting RNAs: Efficient tools to inactivate oncogenic mutations and restore p53 pathways
Martinez, L. A., Naguibneva, I., Lehrmann, H., Vervisch, A., Tchénio, T., Lozano, G., & Harel-Bellan, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222406899 · Cited by 210 · see citing works
The molecular pathogenesis of hereditary and sporadic adrenocortical and adrenomedullary tumors
Koch, C. A., Pacak, K., & Chrousos, G. P. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021069 · Cited by 177 · see citing works
Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation
Figueiredo, B. C., Sandrini, R., Zambetti, G. P., Pereira, R. M., Cheng, C., Liu, W., Lacerda, L., Pianovski, M. A., Michalkiewicz, E., Jenkins, J., et al. (2006) · Journal of Medical Genetics · doi:10.1136/jmg.2004.030551 · Cited by 166 · see citing works
Genome Stability Requires p53
Eischen, C. M. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026096 · Cited by 161 · see citing works
Detailed haplotype analysis at the TP53 locus in p.R337H mutation carriers in the population of Southern Brazil: evidence for a founder effect
Garritano, S., Gemignani, F., Palmero, E. I., Olivier, M., Martel-Planche, G., Le Calvez-Kelm, F., Brugiéres, L., Vargas, F. R., Brentani, R. R., Ashton-Prolla, P., et al. (2010) · Human Mutation · doi:10.1002/humu.21151 · Cited by 153 · see citing works
Osteosarcoma: Molecular Pathogenesis and iPSC Modeling
Lin, Y.-H., Jewell, B. E., Gingold, J., Lu, L., Zhao, R., Wang, L. L., & Lee, D.-F. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.06.004 · Cited by 150 · see citing works
p53 Mutations in sporadic adrenocortical tumors
Ohgaki, H., Kleihues, P., & Heitz, P. U. (1993) · International Journal of Cancer · doi:10.1002/ijc.2910540310 · Cited by 139 · see citing works
The p53 pathway in hematopoiesis: lessons from mouse models, implications for humans
Pant, V., Quintás-Cardama, A., & Lozano, G. (2012) · Blood · doi:10.1182/blood-2012-05-356014 · Cited by 129 · see citing works
Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3
LeBron, C., Chen, L., Gilkes, D. M., & Chen, J. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601032 · Cited by 122 · see citing works
A Polymorphic p53 Response Element in KIT Ligand Influences Cancer Risk and Has Undergone Natural Selection
Zeron-Medina, J., Wang, X., Repapi, E., Campbell, M. R., Su, D., Castro-Giner, F., Davies, B., Peterse, E. F. P., Sacilotto, N., Walker, G. J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.017 · Cited by 118 · see citing works
A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations: Table 1
Wilson, J. R. F., Bateman, A. C., Hanson, H., An, Q., Evans, G., Rahman, N., Jones, J. L., & Eccles, D. M. (2010) · Journal of Medical Genetics · doi:10.1136/jmg.2010.078113 · Cited by 122 · see citing works
Proteolytic Cleavage of the mdm2 Oncoprotein during Apoptosis
Chen, L., Marechal, V., Moreau, J., Levine, A. J., & Chen, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22966 · Cited by 121 · see citing works
Regulation of DNA damage recognition and nucleotide excision repair: another role for p53
Ford, J. M. (2005) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2005.04.005 · Cited by 117 · see citing works
Clonal analysis of human adrenocortical carcinomas and secreting adenomas
Gicquel, C., Leblond‐Francillard, M., Bertagna, X., Louvel, A., Chapuls, Y., Luton, J., Girard, F., & Le Bouc, Y. (1994) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1994.tb02485.x · Cited by 111 · see citing works
Tumor Syndromes Predisposing to Osteosarcoma
Hameed, M., & Mandelker, D. (2018) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000190 · Cited by 109 · see citing works
Mutant p53 promotes tumor progression and metastasis by the endoplasmic reticulum UDPase ENTPD5
Vogiatzi, F., Brandt, D. T., Schneikert, J., Fuchs, J., Grikscheit, K., Wanzel, M., Pavlakis, E., Charles, J. P., Timofeev, O., Nist, A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612711114 · Cited by 99 · see citing works
Human DNA damage response and repair deficiency syndromes: linking genomic instability and cell cycle checkpoint proficiency
Kerzendorfer, C., & O’Driscoll, M. (2009) · DNA Repair · doi:10.1016/j.dnarep.2009.04.018 · Cited by 97 · see citing works
Mutant p53 drives cancer chemotherapy resistance due to loss of function on activating transcription of PUMA
Huang, Y., Liu, N., Liu, J., Liu, Y., Zhang, C., Long, S., Luo, G., Zhang, L., & Zhang, Y. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1688951 · Cited by 94 · see citing works
At-Risk Populations for Osteosarcoma: The Syndromes and Beyond
Calvert, G. T., Randall, R. L., Jones, K. B., Cannon-Albright, L., Lessnick, S., & Schiffman, J. D. (2012) · Sarcoma · doi:10.1155/2012/152382 · Cited by 90 · see citing works
Towards an understanding of the role of p53 in adrenocortical carcinogenesis
Wasserman, J. D., Zambetti, G. P., & Malkin, D. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.09.010 · Cited by 84 · see citing works
Self-citation
Genetics of tumors of the adrenal cortex
Bonnet-Serrano, F., & Bertherat, J. (2018) · Endocrine Related Cancer · doi:10.1530/erc-17-0361 · Cited by 80 · see citing works
Carney complex with adrenal cortical carcinoma
Morin, E., Mete, O., Wasserman, J. D., Joshua, A. M., Asa, S. L., & Ezzat, S. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2321 · Cited by 69 · see citing works
p53 protein accumulation and gene mutations in human glioma cell lines
Anker, L., Ohgaki, H., Ludeke, B. I., Herrmann, H., Kleihues, P., & Westphal, M. (1993) · International Journal of Cancer · doi:10.1002/ijc.2910550618 · Cited by 66 · see citing works
Radiation therapy and secondary malignancy in Li‐Fraumeni syndrome: A hereditary cancer registry study
Hendrickson, P. G., Luo, Y., Kohlmann, W., Schiffman, J., Maese, L., Bishop, A. J., Lloyd, S., Kokeny, K. E., Hitchcock, Y. J., Poppe, M. M., et al. (2020) · Cancer Medicine · doi:10.1002/cam4.3427 · Cited by 64 · see citing works
Mutation analysis of the CHK2 gene in breast carcinoma and other cancers
Ingvarsson, S., Sigbjornsdottir, B. I., Huiping, C., Hafsteinsdottir, S. H., Ragnarsson, G., Barkardottir, R. B., Arason, A., Egilsson, V., & Bergthorsson, J. T. (2002) · Breast Cancer Research · doi:10.1186/bcr435 · Cited by 63 · see citing works
Molecular epidemiology of adrenocortical tumors in southern Brazil
Custódio, G., Komechen, H., Figueiredo, F. R. O., Fachin, N. D., Pianovski, M. A. D., & Figueiredo, B. C. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.10.019 · Cited by 63 · see citing works
Retinoblastoma tumor suppressor and genome stability
(2002) · Advances in Cancer Research · doi:10.1016/s0065-230x(02)85002-3 · Cited by 48 · see citing works
Identification of a common polymorphism in the TopBP1 gene associated with hereditary susceptibility to breast and ovarian cancer
Karppinen, S.-M., Erkko, H., Reini, K., Pospiech, H., Heikkinen, K., Rapakko, K., Syväoja, J. E., & Winqvist, R. (2006) · European Journal of Cancer · doi:10.1016/j.ejca.2006.05.030 · Cited by 42 · see citing works
Protecting the genome from mdm2 and mdmx
Melo, A. N., & Eischen, C. M. (2012) · Genes & Cancer · doi:10.1177/1947601912454139 · Cited by 20 · see citing works
Nearly Half of TP53 Germline Variants Predicted To Be Pathogenic in Patients With Osteosarcoma Are De Novo: A Report From the Children’s Oncology Group
Diessner, B. J., Pankratz, N., Hooten, A. J., Mirabello, L., Sarver, A. L., Mills, L. J., Malkin, D., Kelley, A. C., & Spector, L. G. (2020) · JCO Precision Oncology · doi:10.1200/po.20.00087 · Cited by 16 · see citing works
Self-citation

Assessing the underlying pattern of human germline mutations: lessons from the factor IX gene
Sommer, S. S. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.10.1634040 · Cited by 42 · see citing works
Prevalence and penetrance of Li-Fraumeni cancer predisposition syndrome
Chan, C. S. (2017) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2016.12.015 · Cited by 10 · see citing works
Germline mutations of the p53 tumor-suppressor gene in cancer-prone families: a review.
Soussi, T., Leblanc, T. M., Baruchel, A., et al. (1993) · PubMed · Cited by 6 · see citing works
A novel germline mutation of TP53 with breast cancer diagnosed as Li–Fraumeni syndrome
Kai, M., Kubo, M., Shikada, S., et al. (2022) · Surgical Case Reports · doi:10.1186/s40792-022-01546-y · Cited by 1 · see citing works
Identification of five new families strengthens the link between childhood choroid plexus carcinoma and germline TP53 mutations
Krutilkova, V., Trková, M., Fleitz, J. M., Gregor, V., Novotna, K., Křepelová, A., Sumerauer, D., Kodet, R., Širůčková, S., Plevová, P., et al. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2005.01.026 · Cited by 97 · see citing works

Authors: Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., & Friend, S. H.
Affiliations: Harvard University (US)
National Institutes of Health (US)
The University of Texas MD Anderson Cancer Center (US)
ORCID: Malkin, David
Strong, Louise C.
Kim, David H.
Tainsky, Michael A.
Friend, Stephen H.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1990-11-30
Volume: 250
Issue: 4985
Pages: 1233-1238
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1978757
OpenAlex: W2005542290
Cited by: 3,765
References: 34
Citations by year: 2026: 36 · 2025: 59 · 2024: 66 · 2023: 65 · 2022: 66 · 2021: 101 · 2020: 100 · 2019: 75 · 2018: 79 · 2017: 103 · 2016: 108 · 2015: 96 · 2014: 103 · 2013: 83 · 2012: 107
FWCI: 76.84
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Public Health Service (34936)
National Cancer Institute (5-T32-CA09299, T32CA009299)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Keywords: Li-Fraumeni syndrome, p53, germline mutations, tumor suppressor, hereditary cancer, sarcoma, breast cancer, childhood tumors, candidate genes
MeSH terms: Amino Acid Sequence, Base Sequence, Breast Neoplasms, Chromosomes, Human, Pair 17, Cloning, Molecular, Codon, DNA, Genetic Testing, Germ Cells, Humans, Molecular Sequence Data, Mutation, Neoplastic Syndromes, Hereditary, Pedigree, Repetitive Sequences, Nucleic Acid, Polymorphism, Restriction Fragment Length, Sarcoma, Deoxyribonucleases, Type II Site-Specific, Polymerase Chain Reaction, Genes, p53, Tumor Suppressor Protein p53

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Germ Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks